PMID- 11720897
OWN - NLM
STAT- MEDLINE
DCOM- 20020111
LR  - 20190906
IS  - 0804-4643 (Print)
IS  - 0804-4643 (Linking)
VI  - 145
IP  - 6
DP  - 2001 Dec
TI  - Leptin, insulin sensitivity and growth hormone binding protein in chronic heart 
      failure with and without cardiac cachexia.
PG  - 727-35
AB  - OBJECTIVE: Regulation of growth hormone (GH) receptor expression and hence tissue 
      GH sensitivity may be important for the conflicting results found in treatment 
      studies with recombinant growth hormone in chronic heart failure (CHF). Growth 
      hormone-binding protein (GHBP) corresponds to the extracellular domain of the GH 
      receptor and is closely related to measures of body composition and, 
      specifically, to size of visceral fat tissue. Leptin, the adipocyte specific (ob) 
      gene product, has been proposed as the signal linking adipose tissue and 
      GHBP/GH-receptor expression. CHF has recently been shown to be a hyperleptinaemic 
      and insulin-resistant state regardless of aetiology. This study aimed to examine 
      the influence of leptin on GHBP in CHF patients with and without cardiac cachexia 
      compared with healthy control subjects. METHODS: We studied 47 male patients with 
      CHF (mean age 61+/-2 years, New York Heart Association (NYHA)-class 2.7+/-0.1, 
      left ventricular ejection fraction (LVEF) 28+/-2%, peak oxygen consumption 
      16.8+/-0.9 ml/kg/min) and 21 male healthy controls of similar age. Of the CHF 
      patients, 19 were cachectic (cCHF; non-oedematous weight loss >7.5% over at least 
      6 months) and 28 non-cachectic (ncCHF; similar for age and LVEF). Insulin 
      sensitivity was assessed by an intravenous glucose tolerance test using the 
      minimal model approach. RESULTS: Compared with healthy controls, patients had 
      elevated levels of leptin (7.6+/-0.7 vs 4.8+/-0.7 ng/ml, P<0.05), insulin 
      (76.2+/-8.9 vs 41.4+/-6.0 pmol/l, P<0.01), and reduced insulin sensitivity 
      (2.43+/-0.2 vs 3.48+/-0.3 min(-1).microU.ml(-1).10(4), P<0.005) but similar GHBP 
      levels (901+/-73 vs 903+/-95 pmol/l). Leptin levels were increased in ncCHF 
      (9.11+/-1.0 ng/ml, P=0.001) but were not different from normal in cCHF 
      (5.32+/-0.7 ng/ml, P>0.5). After correction for total body fat mass, both ncCHF 
      and cCHF were hyperleptinaemic (41.8+/-3.8 and 37.9+/-0.38 vs 24.4+/-2.1 
      ng/ml/100 g, ANOVA P=0.001). In both patients and controls there was a direct 
      correlation between leptin levels and GHBP (r=0.70 and r=0.71 respectively, both 
      P<0.0001). This relationship was stronger than between GHBP and several 
      parameters of body composition (body mass index (BMI), total and regional body 
      fat mass or % body fat) and held true when sub-groups were tested individually 
      (ncCHF r=0.62, P<0.001; cCHF r=0.79, P<0.0001). In multivariate regression 
      analysis in all CHF patients, serum leptin levels emerged as the strongest 
      predictor of GHBP, independent of age, BMI, total and regional fat mass or % body 
      fat, fasting insulin level and insulin sensitivity. CONCLUSION: Fat mass 
      corrected leptin levels are elevated in CHF patients with and without cachexia. 
      Reduced total fat mass may account for lower leptin levels in cachectic CHF 
      patients compared with non cachectic patients. Leptin strongly predicts GHBP 
      levels in CHF regardless of its hyperleptinaemic state or severely altered body 
      composition as in cardiac cachexia. Leptin could be the signalling link between 
      adipose tissue and GHBP/GH receptor expression in CHF.
FAU - Doehner, W
AU  - Doehner W
AD  - Department of Clinical Cardiology, NHLI, Imperial College School of Medicine, 
      London, UK. w.doehner@ic.ac.uk
FAU - Pflaum, C D
AU  - Pflaum CD
FAU - Rauchhaus, M
AU  - Rauchhaus M
FAU - Godsland, I F
AU  - Godsland IF
FAU - Egerer, K
AU  - Egerer K
FAU - Cicoira, M
AU  - Cicoira M
FAU - Florea, V G
AU  - Florea VG
FAU - Sharma, R
AU  - Sharma R
FAU - Bolger, A P
AU  - Bolger AP
FAU - Coats, A J
AU  - Coats AJ
FAU - Anker, S D
AU  - Anker SD
FAU - Strasburger, C J
AU  - Strasburger CJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Eur J Endocrinol
JT  - European journal of endocrinology
JID - 9423848
RN  - 0 (Carrier Proteins)
RN  - 0 (Insulin)
RN  - 0 (Leptin)
RN  - W06KFL3RDT (somatotropin-binding protein)
SB  - IM
MH  - Adipose Tissue
MH  - Body Composition
MH  - Body Mass Index
MH  - Cachexia/*etiology
MH  - Cardiac Output, Low/complications/*physiopathology
MH  - Carrier Proteins/*blood
MH  - Chronic Disease
MH  - Fasting
MH  - Glucose Tolerance Test
MH  - Humans
MH  - Insulin/blood/*pharmacology
MH  - Leptin/*blood
MH  - Male
MH  - Middle Aged
MH  - Oxygen Consumption
MH  - Regression Analysis
MH  - Ventricular Function, Left
MH  - Weight Loss
EDAT- 2001/11/27 10:00
MHDA- 2002/01/12 10:01
CRDT- 2001/11/27 10:00
PHST- 2001/11/27 10:00 [pubmed]
PHST- 2002/01/12 10:01 [medline]
PHST- 2001/11/27 10:00 [entrez]
AID - 145727 [pii]
AID - 10.1530/eje.0.1450727 [doi]
PST - ppublish
SO  - Eur J Endocrinol. 2001 Dec;145(6):727-35. doi: 10.1530/eje.0.1450727.